当前位置: X-MOL 学术Exp. Cell Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
GRWD1 promotes cell proliferation and migration in non-small cell lung cancer by activating the Notch pathway.
Experimental Cell Research ( IF 3.7 ) Pub Date : 2019-12-28 , DOI: 10.1016/j.yexcr.2019.111806
Qiongzi Wang 1 , Hongjiu Ren 1 , Yitong Xu 1 , Jun Jiang 1 , Muli Wudu 1 , Zongang Liu 2 , Hongbo Su 1 , Xizi Jiang 1 , Yao Zhang 1 , Bo Zhang 1 , Xueshan Qiu 1
Affiliation  

GRWD1 is a member of the WD repeat protein family that is over-expressed in various cancer cell lines and associated with poor prognosis in patients with cancer. However, its biological function and mechanism in non-small cell lung cancer (NSCLC) remain unclear. In this study, we aimed to elucidate the role of GRWD1 in NSCLC. Immunohistochemistry on tumor specimens from 170 patients showed that GRWD1 is highly expressed in NSCLC tissues and positively correlated with tumor size, lymph node metastasis, and P-TNM stage, but negatively correlated with differentiation and prognosis. We found that GRWD1 promotes cell colony formation by affecting the expression of Cyclin B1, CDK1, and p27 and inducing G2/M transition. GRWD1 was also found to stimulate cell migration through RhoA, RhoC, and CDC42, and induce epithelial-mesenchymal transition by affecting the expression of E-cadherin, N-cadherin, Vimentin, Snail, Zeb1, and ZO-1. Our results indicated that the GRWD1 can activate the Notch signaling pathway by affecting the Notch intracellular domain and promoting the expression of Hes1. Our use of DAPT to suppress Notch signaling confirmed that GRWD1 promotes the progression of NSCLC through the Notch signaling pathway and may be a potential prognostic biomarker and therapeutic target for this disease.

中文翻译:

GRWD1通过激活Notch途径促进非小细胞肺癌中的细胞增殖和迁移。

GRWD1是WD重复蛋白家族的成员,该蛋白在各种癌细胞系中过表达,并且与癌症患者的预后不良相关。然而,其在非小细胞肺癌(NSCLC)中的生物学功能和机制仍不清楚。在这项研究中,我们旨在阐明GRWD1在NSCLC中的作用。对170例患者的肿瘤标本进行的免疫组织化学分析表明,GRWD1在NSCLC组织中高表达,与肿瘤大小,淋巴结转移和P-TNM分期呈正相关,而与分化和预后呈负相关。我们发现GRWD1通过影响细胞周期蛋白B1,CDK1和p27的表达并诱导G2 / M过渡来促进细胞集落形成。还发现GRWD1通过RhoA,RhoC和CDC42刺激细胞迁移,并通过影响E-cadherin,N-cadherin,波形蛋白,Snail,Zeb1和ZO-1的表达来诱导上皮-间质转化。我们的结果表明GRWD1可以通过影响Notch细胞内结构域并促进Hes1的表达来激活Notch信号通路。我们使用DAPT抑制Notch信号转导证实了GRWD1通过Notch信号转导通路促进了NSCLC的发展,并且可能是该疾病的潜在预后生物标志物和治疗靶标。
更新日期:2019-12-29
down
wechat
bug